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Publication Abstract from PubMed

A systematic and robust approach to generating complex protein nanomaterials would have broad utility. We develop a hierarchical approach to designing multi-component protein assemblies from two classes of modular building blocks: designed helical repeat proteins (DHRs) and helical bundle oligomers (HBs). We first rigidly fuse DHRs to HBs to generate a large library of oligomeric building blocks. We then generate assemblies with cyclic, dihedral, and point group symmetries from these building blocks using architecture guided rigid helical fusion with new software named WORMS. X-ray crystallography and cryo-electron microscopy characterization show that the hierarchical design approach can accurately generate a wide range of assemblies, including a 43 nm diameter icosahedral nanocage. The computational methods and building block sets described here provide a very general route to de novo designed protein nanomaterials.

Design of multi-scale protein complexes by hierarchical building block fusion.,Hsia Y, Mout R, Sheffler W, Edman NI, Vulovic I, Park YJ, Redler RL, Bick MJ, Bera AK, Courbet A, Kang A, Brunette TJ, Nattermann U, Tsai E, Saleem A, Chow CM, Ekiert D, Bhabha G, Veesler D, Baker D Nat Commun. 2021 Apr 16;12(1):2294. doi: 10.1038/s41467-021-22276-z. PMID:33863889^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.